Modelado numérico de la propagación de fractura por fatiga utilizando el método de los elementos de contorno

The work presents a computer tool based on the boundary element method (BEM), that allows the study of the propagation of fracture phenomenon in structures which have sustained cyclical efforts. The code functions to develop computer models focused on the study of residual resistance of fractured bi-dimensional components based on linear elastic fracture mechanics (LEFM). The boundary element formulation of the problem is presented, as well as its computer implementation and its application to the specific problem analysis of fracture growth by fatigue. Fracture growth is modeled through the theory proposed by Paris, applied to the case of flat elasticity, and the criteria of maximum main efforts is used to define the direction of propagation (Portela, 1992). The BEM formulation was implemented in a computer code developed in Matlab 7.0 . The program has demonstrated effectiveness in predicting trajectories of propagation and residual resistance by fatigue, allowing its use as a tool of analysis in engineering.El trabajo presenta una herramienta computacional basada en el método de los elementos de contorno, (boundary element method –BEM–), que permite estudiar el fenómeno de propagación de fractura en estructuras sometidas a esfuerzos cíclicos. El código sirve para desarrollar modelos computacionales enfocados al estudio de resistencia residual de componentes bidimensionales fracturados, basados en la mecánica de la fractura lineal elástica, (linear elastic fracture mechanics –LEFM–). Se presenta la formulación por elementos de contorno del problema, su implementación computacional y su aplicación al análisis de problemas específicos de crecimiento de fractura por fatiga. El crecimiento de la fractura es modelado a través de la teoría propuesta por Paris, aplicada al caso de elasticidad plana, y es usado el criterio de esfuerzos principales máximos para definir la dirección de propagación (Portela, 1992). La formulación BEM fue implementada en un código computacional desarrollado en Matlab 7.0 . El programa ha demostrado efectividad para predecir trayectorias de propagación y resistencia residual por fatiga, permitiendo su uso como herramienta de análisis en ingeniería

In vitro–in vivo correlation of drug release profiles from medicated contact lenses using an in vitro eye blink model

There is still a paucity of information on how in vitro release profiles from drug-loaded contact lenses (CLs) recorded in 3D printed eye models correlate with in vivo profiles. This work aims to evaluate the release profiles of two drug-loaded CLs in a 3D in vitro eye blink model and compare the obtained results with the release in a vial and the drug levels in tear fluid previously obtained from an animal in vivo study. In vitro release in the eye model was tested at two different flow rates (5 and 10 µL/min) and a blink speed of 1 blink/10 s. Model CLs were loaded with two different drugs, hydrophilic pravastatin and hydrophobic resveratrol. The release of both drugs was more sustained and lower in the 3D eye model compared to the in vitro release in vials. Interestingly, both drugs presented similar release patterns in the eye model and in vivo, although the total amount of drugs released in the eye model was significantly lower, especially for resveratrol. Strong correlations between percentages of pravastatin released in the eye model and in vivo were found. These findings suggest that the current 3D printed eye blink model could be a useful tool to measure the release of ophthalmic drugs from medicated CLs. Nevertheless, physiological parameters such as the composition of the tear fluid and eyeball surface, tear flow rates, and temperature should be optimized in further studiesOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This project was funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Actions grant agreement N° 813440 (ORBITAL–Ocular Research by Integrated Training And Learning). The work was also partially supported by MCIN [PID 2020-113881RB-I00/AEI/10.13039/501100011033], Spain, Xunta de Galicia [ED431C 2020/17], FEDER, and the Hong Kong Special Administrative Region Government and InnoHK. M. Vivero-Lopez acknowledges Xunta de Galicia (Consellería de Cultura, Educación e Ordenación Universitaria) for a predoctoral research fellowship [ED481A-2019/120]. P. Garg acknowledges the support of the Collaborative Research and Training Experience (CREATE) Program awarded by the Natural Sciences and Engineering Research Council of Canada (NSERC)S

Interpersonal communication about pictorial health warnings on cigarette packages: Policy-related influences and relationships with smoking cessation attempts

This study evaluated the relationship between interpersonal communication about cigarette health warning labels (HWLs), psychological responses to HWLs, and smoking cessation attempts. Data were analyzed from online consumer panels of adult smokers in Australia, Canada and Mexico, during implementation of new pictorial health warning labels (HWLs) on cigarette packs. Approximately 1000 adult smokers were surveyed in each country every four months (September 2012, January 2013, May 2013, September 2013, January 2014). Only smokers followed for at least two waves were included in the analytic sample. Participants reported the frequency of talking about HWLs in the last month (in general, with family members, and with friends). For each country, poisson generalized estimating equation (GEE) models were estimated to assess the bivariate and adjusted correlates of talking about HWLs. Logistic GEE models regressed having attempted to quit by the subsequent wave on HWL talk, socio-demographics and psychological responses to HWLs. The frequency of HWL talk gradually decreased in Canada (48%–36%) after new HWLs were implemented; an increase (30%–58%) in Australia corresponded with implementation of new HWLs, after which talking stabilized; and the frequency of HWL talk in Mexico was stable over time, where new HWLs are implemented every six months. Talk about HWLs was an independent predictor of subsequent quit attempts in Canada (AOR = 1.50; 95% CI = 1.11 –2.02), Australia (AOR = 1.41; 95% CI = 1.05–1.89), and Mexico (AOR = 1.53; 95% CI = 1.11–2.10), as was cognitive responses to HWLs (Australia AOR = 1.66; 95% CI = 1.22–2.24; Canada AOR = 1.56; 95% CI = 1.15–2.11; Mexico AOR = 1.30; 95% CI = 0.91–1.85). No interaction between talk and cognitive reactions to HWLs were found. These results suggest that interpersonal communication about HWLs influences smoking cessation attempts independent of other established predictors of smoking cessation, including cessation-related HWL responses. Future research should determine ways to catalyze interpersonal communication about HWLs and thereby potentiate HWL effects

Phosphorylcholine-Based Contact Lenses for Sustained Release of Resveratrol: Design, Antioxidant and Antimicrobial Performances, and In Vivo Behavior

Design of advanced contact lenses (CLs) demands materials that are safe and comfortable for the wearers and that preserve the normal eye microbiota, avoiding chronic inflammation and biofilm development. This work aimed to combine the natural antibiofouling phosphorylcholine and the antioxidant and prebiotic resveratrol as integral components of CLs that may have the additional performance of preventing oxidative-stress related eye diseases. Different from previous uses of 2-methacryloyloxyethyl phosphorylcholine (MPC) as coating, we explored the feasibility of adding MPC at high proportions as a comonomer of 2-hydroxyethyl methacrylate (HEMA)-based hydrogels while still allowing for the loading of the hydrophobic resveratrol. Homogeneous distribution of MPC along the hydrogel depth (confirmed by Raman spectroscopy) notably increased solvent uptake and the proportion of free water while it decreased Young’s modulus. Relevantly, MPC did not hinder the uptake of resveratrol by CLs (>10 mg/g), which indeed showed network/water partition coefficients of >100. Protocols for CLs sterilization and loading of resveratrol under aseptic conditions were implemented, and the effects of tear proteins on resveratrol release rate were investigated. CLs sustained resveratrol release for more than 24 h in vitro, and sorption of albumin onto the hydrogel, although attenuated by MPC, slowed down the release. The combination of MPC and resveratrol reduced P. aeruginosa and S. aureus growth as tested in a novel hydrogel disk-agar interface biofilm growth setup. The developed CLs showed excellent anti-inflammatory properties and biocompatibility in in ovo and rabbit tests and provided higher and more prolonged levels of resveratrol in tear fluid, which favored resveratrol biodistribution in anterior and posterior eye segments compared to eye drops. Correlations between the release profiles of resveratrol in vitro and in vivo were assessed. Relevantly, the CLs preserved the antioxidant properties of resveratrol during the entire 8 h of wearing. In sum, CLs prepared with high proportion in MPC may help address safety and comfort requirements while having drug releasing capabilitiesThe authors are grateful to Mabel Loza and Cristina Val García, from BioFarma Research Group (USC GI-1685), for their help in the UPLC experiment, and to Luis Díaz-Gómez for advice in the anti-inflammatory tests. M.V.-L. acknowledges Xunta de Galicia (Consellería de Cultura, Educación e Ordenación Universitaria) for a predoctoral research fellowship [Grant ED481A-2019/120]. A.F.P.-d.-M. is an ESR of the European Union’s Horizon 2020 research and innovation program under Marie Skłodowska-Curie Actions Grant Agreement 813440 (ORBITAL-Ocular Research by Integrated Training and Learning)S

Cigarette brands with flavour capsules in the filter: Trends in use and brand perceptions among smokers in the USA, Mexico and Australia, 2012-2014

Objective To describe trends, correlates of use and consumer perceptions related to the product design innovation of flavour capsules in cigarette filters.  Methods Quarterly surveys from 2012 to 2014 were analysed from an online consumer panel of adult smokers aged 18–64, living in the USA (n=6865 observations; 4154 individuals); Mexico (n=5723 observations; 3366 individuals); and Australia (n=5864 observations; 2710 individuals). Preferred brand varieties were classified by price (ie, premium; discount) and flavour (ie, regular; flavoured without capsule; flavoured with capsule). Participants reported their preferred brand variety's appeal (ie, satisfaction; stylishness), taste (ie, smoothness, intensity), and harm relative to other brands and varieties. GEE models were used to determine time trends and correlates of flavour capsule use, as well as associations between preferred brand characteristics (ie, price stratum, flavour) and perceptions of relative appeal, taste and harm.  Results Preference for flavour capsules increased significantly in Mexico (6% to 14%) and Australia (1% to 3%), but not in the USA (4% to 5%). 18–24 year olds were most likely to prefer capsules in the USA (10%) and Australia (4%), but not Mexico. When compared to smokers who preferred regular brands, smokers who preferred brands with capsules viewed their variety of cigarettes as having more positive appeal (all countries), better taste (all countries), and lesser risk (Mexico, USA) than other brand varieties.  Conclusions Results indicate that use of cigarettes with flavour capsules is growing, is associated with misperceptions of relative harm, and differentiates brands in ways that justify regulatory action

Exposure of Secondary School Adolescents from Argentina and Mexico to Smoking Scenes in Movies: a Population-based Estimation

Introducción: Las escenas de consumo de tabaco en películas promueve el inicio del tabaquismo en adolescentes, por lo que el análisis de la cantidad de imágenes de tabaco en películas que realmente llega a los adolescentes se ha convertido en un tema de interés creciente.Objetivo: Estimar el nivel de exposición a imágenes de tabaco contenidas en películas vistas por adolescentes de la Argentina y México.Material y métodos: Se realizó una encuesta a alumnos de primer año de nivel secundario de la Argentina y México. Se analizaron las 100 películas con mayor recaudación en cada año del período 2009-2013 (Argentina) y 2010-2014 (México).A cada participante se le asignó una muestra aleatoria de 50 de estas películas, preguntándosele si la había visto. Se estimó el número total de adolescentes que habían visto cada película en cada país y se multiplicó por el número de escenas que contenían tabaco (ocurrencias) en cada película para así obtener el número de impresiones crudas de tabaco vistas por los adolescentes escolarizados de cada país.Resultados: Se analizaron 422 films en la Argentina y 433 en México. Más de 500 millones de imágenes de tabaco fueron vistas por la población joven de cada país, lo que promedia 128 y 121 minutos de escenas con tabaquismo por cada adolescente en la Argentina y México, respectivamente. Si bien los films calificados para mayores de 15/16/18 años tenían mayor promedio por película de escenas de tabaco, las películas calificadas para menores de esta edad fueron responsables de la mayor cantidad de escenas de tabaquismo vistas por adolescentes (67,3% en la Argentina y 54,4% en México) debido a su mayor audiencia.Conclusión: A nivel poblacional, las películas para niños son las máximas responsables de la carga de tabaco vista por adolescentes.Background: Smoking scenes in movies promote adolescent smoking onset; thus, the analysis of the number of images of smoking in movies really reaching adolescents has become a subject of increasing interest. Objective: The aim of this study was to estimate the level of exposure to images of smoking in movies watched by adolescents in Argentina and Mexico. Methods: First-year secondary school students from Argentina and Mexico were surveyed. One hundred highest-grossing films from each year of the period 2009-2013 (Argentina) and 2010-2014 (Mexico) were analyzed. Each participant was assigned a random sample of 50 of these movies and was asked if he/she had watched them. The total number of adolescents who had watched each movie in each country was estimated and was multiplied by the number of smoking scenes (occurrences) in each movie to obtain the number of gross smoking impressions seen by secondary school adolescents from each country. Results: Four-hundred and twenty-two movies were analyzed in Argentina and 433 in Mexico. Exposure to more than 500 million smoking impressions was estimated for adolescents in each country, averaging 128 and 121 minutes of smoking scenes seen by each Argentine and Mexican adolescent, respectively. Although 15, 16 and 18-rated movies had more smoking scenes in average, movies rated for younger teenagers were responsible for the highest number of smoking scenes watched by the students (67.3% in Argentina and 54.4% in Mexico) due to their larger audience. Conclusion: At the population level, movies aimed at children are responsible for the highest tobacco burden seen by adolescents.Fil: Salgado, Maria Victoria. Centro de Estudios de Estado y Sociedad; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pérez, Adriana Alicia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Centro de Estudios de Estado y Sociedad; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Abad Vivero, Erika N. Instituto Nacional de Salud Pública; MéxicoFil: Thrasher, James F.. Instituto Nacional de Salud Pública; México. University Of South Carolina; Estados UnidosFil: Sargent, James D.. Geisel School Of Medicine At Dartmouth; Estados UnidosFil: Mejia, Raul Mariano. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Centro de Estudios de Estado y Sociedad; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Long-term antibiotic therapy in patients with surgery-indicated not undergoing surgery infective endocarditis

Background: To date, there is little information regarding management of patients with infective endocarditis (IE) that did not undergo an indicated surgery. Therefore, we aimed to evaluate prognosis of these patients treated with a long-term antibiotic treatment strategy, including oral long term suppressive antibiotic treatment in five referral centres with a multidisciplinary endocarditis team. Methods: This retrospective, multicenter study retrieved individual patient-level data from five referral centres in Spain. Among a total of 1797, 32 consecutive patients with IE were examined (median age 72 years; 78% males) who had not undergone an indicated surgery, but received long-term antibiotic treatment (LTAT) and were followed by a multidisciplinary endocarditis team, between 2011 and 2019. Primary outcomes were infection relapse and mortality during follow-up. Results: Among 32 patients, 21 had IE associated with prostheses. Of the latter, 8 had an ascending aorta prosthetic graft. In 24 patients, a switch to long-term oral suppressive antibiotic treatment (LOSAT) was considered. The median duration of LOSAT was 277 days. Four patients experienced a relapse during follow-up. One patient died within 60 days, and 12 patients died between 60 days and 3 years. However, only 4 deaths were related to IE. Conclusions: The present study results suggest that a LTAT strategy, including LOSAT, might be considered for patients with IE that cannot undergo an indicated surgery. After hospitalization, they should be followed by a multidisciplinary endocarditis team

Potentiation of 5-fluorouracil encapsulated in zeolites as drug delivery systems for in vitro models of colorectal carcinoma

The studies of potentiation of 5-fluorouracil (5-FU), a traditional drug used in the treatment of several cancers, including colorectal (CRC), were carried out with zeolites Faujasite in the sodium form, with different particle sizes (NaY, 700nm and nanoNaY, 150nm) and Linde type L in the potassium form (LTL) with a particle size of 80nm. 5-FU was loaded into zeolites by liquid-phase adsorption. Characterization by spectroscopic techniques (FTIR, 1H NMR and 13C and 27Al solid-state MAS NMR), chemical analysis, thermal analysis (TGA), nitrogen adsorption isotherms and scanning electron microscopy (SEM), demonstrated the successful loading of 5-FU into the zeolite hosts. In vitro drug release studies (PBS buffer pH 7.4, 37°C) revealed the release of 80-90% of 5-FU in the first 10min. To ascertain the drug release kinetics, the release profiles were fitted to zero-order, first-order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas and Weibull kinetic models. The in vitro dissolution from the drug delivery systems (DDS) was explained by the Weibull model. The DDS efficacy was evaluated using two human colorectal carcinoma cell lines, HCT-15 and RKO. Unloaded zeolites presented no toxicity to both cancer cells, while all DDS allowed an important potentiation of the 5-FU effect on the cell viability. Immunofluorescence studies provided evidence for zeolite-cell internalization.RA is recipient of fellowship SFRH/BI/51118/2010 from Fundacao para a Ciencia e a Tecnologia (FCT, Portugal). This work was supported by the FCT projects refs. PEst-C/QUI/UI0686/2011 and PEst-C/CTM/LA0011/2011 and the Centre of Chemistry and Life and Health Sciences Research Institute (University of Minho, Portugal). The NMR spectrometer is part of the National NMR Network (RNRMN), supported with funds from FCT/QREN (Quadro de Referencia Estrategico Nacional)

Interaction of Mesoporous Silica Nanoparticles with Human Red Blood Cell Membranes: Size and Surface Effects

The interactions of mesoporous silica nanoparticles (MSNs) of different particle sizes and surface properties with human red blood cell (RBC) membranes were investigated by membrane filtration, flow cytometry, and various microscopic techniques. Small MCM-41-type MSNs (∼100 nm) were found to adsorb to the surface of RBCs without disturbing the membrane or morphology. In contrast, adsorption of large SBA-15-type MSNs (∼600 nm) to RBCs induced a strong local membrane deformation leading to spiculation of RBCs, internalization of the particles, and eventual hemolysis. In addition, the relationship between the degree of MSN surface functionalization and the degree of its interaction with RBC, as well as the effect of RBC−MSN interaction on cellular deformability, were investigated. The results presented here provide a better understanding of the mechanisms of RBC−MSN interaction and the hemolytic activity of MSNs and will assist in the rational design of hemocompatible MSNs for intravenous drug delivery and in vivo imaging

Bioresponsive Mesoporous Silica Nanoparticles for Triggered Drug Release

Mesoporous silica nanoparticles (MSNPs) have garnered a great deal of attention as potential carriers for therapeutic payloads. However, achieving triggered drug release from MSNPs in vivo has been challenging. Here, we describe the synthesis of stimulus-responsive polymer-coated MSNPs and the loading of therapeutics into both the core and shell domains. We characterize MSNP drug-eluting properties in vitro and demonstrate that the polymer-coated MSNPs release doxorubicin in response to proteases present at a tumor site in vivo, resulting in cellular apoptosis. These results demonstrate the utility of polymer-coated nanoparticles in specifically delivering an antitumor payload.National Science Foundation (U.S.) (grant R01-CA124427)National Science Foundation (U.S.) (grant U54-CA119349)National Science Foundation (U.S.) (grant U54-CA119335